A Trial to Improve Quality of Life With Stereotactic Body Radiotherapy for Patients With Painful Bone Metastases (ROBOMET)

A Phase III Randomized-controlled, Single-blind Trial to Improve Quality of Life With Stereotactic Body Radiotherapy for Patients With Painful Bone Metastases

This is a phase III randomized-controlled, single-blind study comparing the standard schedule for antalgic radiotherapy of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy (3D-CRT) to a single fraction of 20.0 Gy delivered through stereotactic body radiotherapy (SBRT). The primary aim of this trial is to double the complete response rate. Secondary aims are to compare general response rates, duration of pain response, acute and late toxicity, HRQoL through patient-reported outcome measures (PROMs), pain flare, and re-irradiation need.

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis; Radiotherapy; Metastasis to Bone
• Intervention / Treatment: Radiation: 3D-conformal radiotherapy; Radiation: Stereotactic body radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Piet Dirix, MD PhD; Phone Number: 003234433737; Email: piet.dirix@gza.be
• Study Contact Backup: Name: Carole Mercier, MD; Phone Number: 003234433737; Email: carole.mercier@gza.be

Study Locations

• Belgium
  • Antwerp
    • Wilrijk, Antwerp, Belgium, 2610
      • Radiotherapy department, GZA Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed malignancy.
• Pain score ≥ 2 on a scale from 0 to 10.
• Radiological or (bone) scintigraphic evidence of bone metastasis at the site of pain.
• Lesions ≤ 5cm in largest diameter.
• Per lesion no more than 3 consecutive spine segments involved with one unaffected vertebral body above and below.
• No more than 3 painful lesions needing treatment.
• Life expectancy estimated at > 3 months.
• Patients who have received the information sheet and signed the informed consent form.
• Patients must be willing to comply with scheduled visits, treatment plan, and other study procedures.
• Patients with a public and/or private health insurance coverage.

Exclusion Criteria:

• Myeloma.
• Bone metastasis in previously irradiated sites.
• Previous radioisotope treatment for bone metastases.
• Complicated bone metastasis, i.e. impending and/or existing pathological fracture, spinal cord compression or cauda equina compression [16].
• Patients with significantly altered mental status or with psychological, familial, sociological or geographical condition potential hampering compliance with the study.
• Individual deprived of liberty or placed under guardianship.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single fraction of 8 Gy; The current standard treatment will be prescribed, i.e. a 3D-conformal radiotherapy of a single fraction dose of 8.0 Gy to the metastasis with a planning target volume (PTV) margin for set-up and positioning uncertainties of 1 cm. This can be performed at any linear accelerator.	Radiation: 3D-conformal radiotherapy; In the standard setting, 95% of the PTV should receive 95% of the prescribed dose while near maximum dose (Dnear-max) in the PTV should not exceed 107%. Image-guidance will consist of portal images showing the relevant bony anatomy.
Experimental: Single fraction of 20 Gy; Within the framework of stereotactic body radiotherapy, a single fraction dose of 20.0 Gy will be delivered to the metastasis using a PTV margin of 3-5 mm based on high-precision image-guided radiotherapy (IGRT). Therefore, only linear accelerators with the European Organization for Radiotherapy & Oncology advisory committee on radiation oncology practice (ESTRO-ACROP) specifications for SBRT can be accepted. A risk-adapted approach will be applied, aiming for the highest possible dose no less than 16 Gy, while respecting the tolerances of critical organs at risk (e.g. spinal cord, cauda equina, brainstem etc.).	Radiation: Stereotactic body radiotherapy; Treatment will be prescribed to the periphery of the target, i.e. 80% of the dose should cover 95% of the PTV. The organ at risk (OAR) dose constraints will be in accordance with the recommendations from the report of the American Association of Physicists in Medicine (AAPM) task group 101. Image-guidance will consist of cone-beam CT in combination with 6 degrees of freedom corrections using robotic couch.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain response	Pain response at the treated index site at 1 month after radiotherapy (RT), as defined by the consensus statement.	4 weeks after RT visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of pain flare	Number of participants with increase in pain score of 2 or more above baseline at the treated site with stable OMED, or an increase of 25% or more in OMED compared with baseline with the pain score stable or 1 point above baseline	24-48 hours after radiotherapy
Duration of pain response	Time until pain progression (defined as an increase in pain score of 2 or more above baseline at the treated site with stable daily oral morphine equivalent, or an increase of 25% or more in daily oral morphine equivalent (OMED) compared with baseline with the pain score stable or 1 point above baseline)	2 years after radiotherapy
Re-irradiation need	Need for re-irradiation of the treated lesion	2 years after radiotherapy
Acute toxicity Measured with CTCAE version 5.0	Measured with CTCAE version 5.0	3 months after radiotherapy
Late toxicity Measured with CTCAE version 5.0	Measured with CTCAE version 5.0	2 years after radiotherapy
Impact of treatment on Quality of Life: EORTC quality of life questionnaire (QLQ) BM22	Using the EORTC quality of life questionnaire for Bone Metastases (QLQ BM22) to measure impact of bone metastases on QoL [min score 0 - max score 100]. A high score represents a high level of symptomatology. The score is calculated by applying a linear transformation on the scores to each answer of the 22 question-long questionnaire (cfr. EORTC mannual).	2 years after radiotherapy
Number of Subsequent Serious Skeletal events	Incidence of symptomatic pathologic fractures, radiation or surgery to bone, and spinal cord compression.	2 years after radiotherapy

Collaborators and Investigators

• Sponsor: Cancer Research Antwerp
• Investigators: Study Director: Dirk Verellen, PhD, Iridium Cancer Network

Publications and helpful links

General Publications

• Mercier C, Dirix P, Ost P, Billiet C, Joye I, Vermeulen P, Lievens Y, Verellen D. A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET). BMC Cancer. 2019 Sep 4;19(1):876. doi: 10.1186/s12885-019-6097-z.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2019
• Primary Completion (Actual): October 26, 2023
• Study Completion (Actual): October 26, 2023

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: February 4, 2019
• First Posted (Actual): February 5, 2019

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Bone metastases; Stereotactic Body Radiotherapy; Spinal metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Neoplasms, Second Primary
• Other Study ID Numbers: CTOR18072GZA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No